High-performance microsystem toward closed-loop continuous metabolites monitoring

描述（由申请人提供）：持续代谢物监测的重要性和必要性怎么强调都不过分。体内监测装置的最新发展集中在小型化和新功能材料的探索性使用上。然而，由于大多数生物传感器倾向于随时间漂移和退化，因此开发简单、可靠、按需、原位（并且可能在体内）自校准/自诊断技术是以最小干预进行方便、连续监测的关键障碍。这一“薄弱环节”的可用性将大大提高连续原位体内监测技术的可靠性和便利性。本提案的目的是开发一种新的聚合物流体微系统，用于连续葡萄糖监测，特别强调前所未有的原位自校准/自诊断能力。这将通过利用采用葡萄糖氧化酶（GOD）酶反应的葡萄糖生物传感器的氧依赖性来实现。所提出的集成校准器，传感器和去泡器模块的微系统建立了内部的校准和诊断微环境，最大限度地减少了外部耦合的庞大的水库和流体系统的需要。开发了一种新的全聚合物流体微系统的制造工艺，以集成独特的低温晶片键合、键合后酶固定化和键合后表面功能化过程，以最小化生物污染。该微系统的创新片上功能包括：（1）单点原位自校准（零值校准），（2）提高灵敏度和降低检测限，以及（3）最大限度地减少由背景氧波动和电化学干扰引起的传感器误差。本提案的目的是开发一种新型的葡萄糖传感器系统，以最少的人为干预进行方便、连续的监测。我们预计这项工作可以为智能和自主生物传感器的开发奠定基础，用于连续监测代谢物，特别是糖尿病和重症监护病房患者。这项工作的影响是非常广泛的，因为所提出的方法适用于许多领域的医疗诊断，生物过程监测和环境监测。

DESCRIPTION (provided by applicant): The importance and need for continuous metabolites monitoring cannot be overemphasized. Most recent developments for in vivo monitoring devices have focused on the miniaturization and the exploratory use of new functional materials. As most biosensors, however, tend to drift and degrade over time, the development of a simple, dependable, on-demand, in situ (and possibly in vivo) self-calibration/self- diagnosis technique is a key obstacle for convenient, continuous monitoring with minimum intervention. The availability of this "weak link" would greatly improve the reliability and convenience of continuous in situ, in vivo monitoring technology. The objective of this proposal is to develop a novel polymer fluidic microsystem for continuous glucose monitoring, with special emphasis on an unprecedented in situ self-calibration/self-diagnosis capability. This will be accomplished by utilizing the oxygen dependency of a glucose biosensor that employs the glucose oxidase (GOD) enzyme reaction. The proposed microsystem with integrated calibrator, sensor, and debubbler modules establishes the calibrating and diagnostic microenvironment internally, minimizing the need of externally coupled bulky reservoirs and fluidic systems. A new fabrication process for all-polymer fluidic microsystem is developed to integrate unique procedures of low-temperature wafer bonding, post- bonding enzyme immobilization, and post-bonding surface functionalization to minimize biofouling. Innovative on-chip functionalities of the microsystem include: (1) one-point in situ self-calibration (zero-value calibration), (2) increased sensitivity and lower detection limit, and (3) minimization of sensor errors caused by background oxygen fluctuations and electrochemical interferences. The objective of this proposal is to develop a novel glucose sensor system for convenient, continuous monitoring with minimum human intervention. We anticipate this work can lay a foundation for the development of intelligent and autonomous biosensors for continuous metabolites monitoring, especially for diabetes and intensive care unit patients. The impact of this work is very broad since the proposed approach is applicable to many areas of medical diagnosis, bioprocess monitoring, and environmental monitoring.